1. Field of the Invention
This invention relates to an improved method for the purification of an N-alkylated aspartame derivative, which is a particularly useful sweetening agent.
2. Related Background Art
N-[N-(3,3-dimethylbutyl)-L-xcex1-aspartyl]-L-phenylalanine 1-methyl ester (neotame) is a high potency dipeptide sweetener (about 8000X sweeter than sucrose) that has the formula 
The synthesis of neotame is disclosed in U.S. Pat. No. 5,480,668, U.S. Pat. No. 5,510,508 and U.S. Pat. No. 5,728,862, the disclosure of each of which is incorporated by reference herein. These processes, however, may produce several impurities, including N,N-di(3,3-dimethylbutyl)-L-aspartyl-L-phenylalanine methyl ester (dialkylated aspartame), xcex1-methyl hydrogen-3-(3,3-dimethylbutyl)-2-L-(2,2-dimethylpropyl)-5-oxo-xcex1-L-(phenylmethyl)-1,4(L)-imidazolidine diacetate (dialkylated imidazolidinone), N-[N-(3,3-dimethylbutyl)-L-xcex1-aspartyl]-L-phenylalanine (demethylated xcex1- or xcex2-neotame) and methyl ester of N-[N-(3,3-dimethylbutyl)-L-xcex1-aspartyl]-L-phenylalanine 1-methyl ester (methylated xcex1- or xcex2-neotame). These impurities are represented respectively by the structural formulae: 
The primary impurities generated in the synthesis of N-[N-(3,3-dimethylbutyl)-L-xcex1-aspartyl]-L-phenylalanine 1-methyl ester, i.e., dialkylated aspartame, methyl ester of xcex1-neotame and dialkylated imidazolidinone, have very similar solubilities compared to N-[N-(3,3-dimethylbutyl)-L-xcex1-aspartyl]-L-phenylalanine 1-methyl ester and thus are difficult to remove by crystallization, thereby making it difficult to obtain pure product in high yield.
Since neotame is mainly employed in foods for human consumption, it is extremely important that neotame exist in a highly purified state. Thus, it is clear that there is a need to economically produce pure N-[N-(3,3-dimethylbutyl)-L-xcex1-aspartyl]-L-phenylalanine 1-methyl ester.
This invention is directed to a process of purifying [N-(3,3-dimethylbutyl)-L-xcex1-aspartyl]-L-phenylalanine 1-methyl ester. The process comprises the steps of: (a) washing neotame with water; (b) combining the water washed neotame with an organic solvent to form a slurry; and (c) filtering the slurry to recover purified neotame. The organic solvent of step (b) may be an aqueous organic solvent.
Preferably, the process includes the steps of washing the neotame recovered in step (c) with an organic solvent, which may be the same or different than the organic solvent of step (b) and drying the washed filtered slurry to recover further purified neotame.